On February 5, 2019, FDA issued the guidance document The Least Burdensome Provisions: Concept and Principles (Final Guidance). This version supersedes the prior version in place since October 2002. FDA published a draft of the guidance (Draft Guidance) in December 2017, which we blogged on here.
As in the Draft Guidance, the Final Guidance defines “least burdensome” to be “the minimum amount of information necessary to adequately address a relevant regulatory question or issue through the most efficient manner at the right time.” Final Guidance at 4. The three elements of the definition, the minimum information necessary, the most efficient means, and the right time, continue to be the least burdensome principles discussed in the guidance. Overall, there are not any many differences in the Final Guidance compared to the Draft Guidance.
The seven guiding principles that FDA intends to apply, and industry is also encouraged to apply, when taking a least burdensome approach are unchanged, although additional details are added to their discussions. Related to industry’s least burdensome submission of material, FDA adds in the Final Guidance that “[i]ndustry should not submit information unrelated to the regulatory decision to FDA” and that “[i]ndustry should reference applicable FDA guidance documents where FDA recommendations were considered.” Id. at 8.
It can be a challenge for sponsors to know exactly what will be used in the regulatory decision making as the Agency continues to request new and different information to establish a reasonable assurance of safety and effectiveness or substantial equivalence. For 510(k)s, sponsors are required to include a signed statement that no material fact has been omitted and thus, may question whether omission of a study they performed might be problematic even if it does not seem necessary for regulatory decision making.
Additional examples of FDA’s use of less burdensome approaches have been added. Though not discussed as a problem with the least burdensome provisions, in addition to adding examples, FDA also removed an example from the Draft Guidance of their use of registries initially designed for postmarket surveillance to support expanded indications for vaginal mesh devices. FDA has been criticized for their oversight of these and other implanted devices where reports of safety issues are raised after being placed on the market.
There are several additions to the Final Guidance that should be welcomed by industry. For example, FDA says, “when discussing alternative approaches, FDA intends to take appropriate consideration of the time and resource implications of [their] additional information requests,” and “[t]he type and amount of minimum information requested by FDA can change over time based on new information that the Agency receives and a better understanding of the technology.” Id. at 13, 19. This latter statement is made in the context of FDA’s discussion of “smart regulation,” with examples such as 510(k) exemptions and enforcement discretion provided to support it. However, it often seems that perhaps more often, the changes over time go in the other direction toward requesting new and different data, studies, labeling, and so forth.
The Final Guidance also expands on the discussion of FDA’s intent to use least burdensome principles when contributing to global harmonization efforts and their down classification of devices. The last addition of note is a section titled “Just-in-time testing,” which promotes the “right time principle for IDE applications” allowing certain early feasibility studies to be “based on less nonclinical data than would be expected for a traditional feasibility or pivotal study.” Id. at 22.
While industry may still feel that they are continually being asked for more information, data, and studies to support their devices, the Final Guidance, by way of sharing examples where FDA has used least burdensome approaches, suggests that, in many cases, it could be worse. As noted in the Final Guidance, readers are encouraged to interact with the Agency early on so as to develop least burdensome approaches, especially in situations where their device may have or be perceived to have different risks.